System and methods for treating cancer cells with alternating polarity magnetic fields

ABSTRACT

Systems for destroying or inhibiting cancer cells and other rapidly-dividing cells including an alternating polarity (AP) magnetic field generator and at least one AP electromagnetic coil adapted to be coupled to a target body area, and a controller to control the AP magnetic field generator and at least one AP electromagnetic coil and cause the field generator and coil to apply AP magnetic field having a frequency of 0.5-500 kHz and a field strength of 0.5-5 mT to the target body area to achieve a desired inhibiting effect on cancer cells or other rapidly-dividing cells. Treatments provided by the system may be co-administered with an anti-cancer drug such as a chemotherapy drug, a hormone therapy drug, targeted therapy drugs, immunotherapy drugs, or an angiogenesis inhibitor drug.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 17/827,984, filed May 30, 2022, which is a continuation of U.S.application Ser. No. 17/308,019, filed May 4, 2021, now U.S. Pat. No.11,344,739, which is a continuation of U.S. application Ser. No.16/784,239, filed Feb. 6, 2020, now U.S. Pat. No. 11,027,143, whichclaims the priority benefit of U.S. Provisional Application Ser. No.62/802,685, filed Feb. 7, 2019. This application claims the prioritybenefit of each of the foregoing applications, which are each herebyincorporated by reference in their entirety.

TECHNICAL FIELD

The present invention involves treating rapidly proliferating ordividing cells, such as cancer cells, and more specifically to systemsand methods for selectively inhibiting or destroying rapidly dividingcells by applying an alternating magnetic field having definedcharacteristics to a target area of a patient's body. Some embodimentsof the invention provide a wearable system capable of providing anambulatory therapy to a non-stationary patient by applying a magneticfield to inhibit or destroy rapidly dividing cells to the target bodyarea.

BACKGROUND OF THE INVENTION

Cell division is a reproductive process in all living systems, includingwithout limitation simple one-celled organisms such as bacteria andprotozoa, as well as more complex organisms such as algae, plants, andanimals, including humans. The cell division cycle involves a series ofevents within the cell that leads to a duplication of the DNA of thecell, with one of the duplicate DNA sequences going to each of twodaughter cells. Prokaryotic cells are one-celled organisms that lack anenclosed nucleus and reproduce by a cell division process known asfission. More complex organisms with enclosed nuclei are calledeukaryotes, whose cells asexually reproduce by a three-part celldivision process involving periods known as interphase, mitosis, andcytokinesis. In the reproduction of sexual cells (i.e., egg and sperm)of more complex organisms, mitosis is replaced by meiosis.

During interphase, the parent cell produces nutrients and othercomponents necessary for mitosis, and the DNA is duplicated as looselypacked chromatin. Mitosis involves separation of the duplicated DNA inthe nucleus of the eukaryotic cell into two nuclei, each having acomplete copy of the duplicated DNA. In cytokinesis, the cytoplasm,organelles & cell membrane are divided, forming two daughter cells ofroughly equal size.

The process of mitosis is further divided into the stages of prophase,prometaphase, metaphase, anaphase, and telophase. In prophase, the DNAduplicated during interphase condenses into discrete long, thinchromosomes having two chromatids joined by a centromere. Each cell hastwo centrioles, which move to opposite poles of the cell duringprophase. Microtubules radiate from near the two centrioles toward thecenter of the cell, including some which extend to the chromatids andhelp to separate the two chromatids into separate daughter chromatids.In metaphase, the chromosomes move toward the cell equator and align inthe metaphase plane (or equatorial plane). The daughter chromatidsseparate from each other at the equator during early anaphase by movingalong the microtubule spindle fibers toward the centromeres at oppositepoles of the cell, a process which elongates the cell. In late anaphasethe daughter chromosomes each reach their opposite poles of the cell,and the cell membrane begins to pinch to form the two daughter cells,which is part of cytokinesis, or the process by which the daughter cellsare separated. During telophase, the microtubules continue to lengthenand a new nuclear envelope forms around each of the separated daughterchromosomes, each of which has an identical set of chromosomes, andcytokinesis proceeds with further pinching of the two daughter cellstoward becoming separate entities. By the end of telophase, themicrotubule spindles disappear. Finally, the daughter cells fullyseparate, completing cytokinesis.

Cancer cells and some non-cancerous cells (e.g., non-malignant tumors)proliferate or grow in an uncontrolled manner in contrast to normalcells. In addition to the extra space such tumors or cells occupy, theymay also damage nearby normal cells. Cancer cells may also metastasize,traveling to other locations in the body, where they continue tohyperproliferate and may form new tumors. The rapid growth of tumors andcancer cells results from their rapid rate of cell division compared tonormal cells.

Many effective anti-cancer and anti-tumor therapies are based on thefact that cells in the process of dividing are more sensitive toradiation and many drugs than non-dividing cells. Because tumor cellsdivide much more frequently than normal cells, it is possible, by usingtherapies that act on tumor cells while they are dividing, toselectively damage or destroy them while leaving normal cells—whichdivide less frequently—less affected. However, because many types ofcancer cells are only slightly more susceptible to radiation and/orchemotherapy agents than normal cells, it is not always possible toselectively affect tumor cells while leaving normal cells unaffected.Consequently, many radiation and chemotherapy agents significantlydamage normal cells as well as tumor cells, leading to a significantpatient burden (e.g., pain, scarring, organ damage, blood damage,impaired immune system function, etc.) for even “successful” treatments.

In addition to radiation and chemotherapeutic agents, other therapiesinvolving different modes of action have been used to treat tumor cells,including without limitation ultrasonic and electrical therapies.Electrical currents and electrical fields have been used for decades formedical purposes.

One type of electrical therapy involves applying an electrical currentthrough body tissue separated by two or more conductive electrodes. Thistype of therapy may be used, for example to stimulate or excite muscleor nerve tissue (e.g., pacemakers, defibrillators, neurostimulators) orto generate heat within a desired body tissue (e.g., thermal therapiesto remodel collagen or to ablate tissue). Electrical therapies involvingconductive electrodes may involve direct current or alternating currentat a wide range of frequencies (e.g., less than 1 Hz to above 1 MHz).The energy from electrical currents is delivered to tissue based on theelectrical conductive characteristics (e.g., resistance, capacitance) ofthe tissue. Since these properties are similar for both tumor and normalcells, such therapies affect both tumor and normal cells (e.g.,destroying both by heat if they are within the current path) in the samemanner. At lower frequencies (typically below 20 kHz), the use ofconductive electrodes may be used to stimulate muscle or nerve tissue toactivate muscle or nerve fibers. At frequencies used in many electricaltherapies (e.g., tens of kHz to MHz), stimulation with conductiveelectrodes is too rapid for stimulation signals to propagate throughsuch tissue and the signals are “shorted.”

Another medical use of electrical energy involves the use of insulatedelectrodes to deliver high frequency electrical energy radiatively orinductively to target tissue. For example, radio frequency (RF) ormicrowave energy may be applied radiatively to tissue through the air oranother electrically insulating material separating the electrodes fromthe tissue being treated. The effect of this type of electrical energyon living tissue is based on the dielectric properties of the tissuerather than their conductive characteristics.

More recently, insulated electrodes have been used to treat cancer cellsand other rapidly proliferating cells by applying AC electric fields atfrequencies of 50-500 kHz and electric field strengths of about 10-1000V/m to a target body area that includes such cells. Such therapy isoften referred to as TC (“tumor curing”) field or TTF (“tumor treatmentfield”) therapy. In U.S. Pat. No. 6,868,289, which is herebyincorporated by reference in its entirety, a method and apparatus aredisclosed for destroying rapidly proliferating cells using insulatedelectrodes to generate an electric field. At electric field frequenciesof 50-500 kHz, the cell membranes of the dividing cells act toconcentrate the electric field lines at the cleavage furrow separatingthe two daughter cells of the dividing cell. The high-density field atthe cleavage furrow causes polarized or charged intracellular componentswithin the cell to move toward the high-density field lines at thecleavage furrow, eventually disrupting the cell membrane at the cleavagefurrow, and destroying the dividing daughter cells.

In U.S. Pat. No. 8,019,414, which is hereby incorporated by reference inits entirety, a method of killing or destroying cancer cells isdisclosed that involves applying an electric field together with anothercancer therapy such as radiation or chemotherapy drugs. The electricalfield may be a field such as that disclosed in the '289 patent.

The use of electric fields to destroy cancer cells, while effective atcertain frequencies and electrical field strengths, is limited in manypractical respects. To provide a safe and consistent electrical fieldstrength, the electrodes of systems such as those disclosed in the '298and '414 patents must be in intimate contact with the tissue (e.g.,skin) of the patient at all times during the treatment. To ensure goodcontact with the patient's skin, it may be necessary to shave all hairfrom the skin to which the electrodes are coupled. Because the therapymay be delivered for an extended period of time, the electrodesfrequently cause skin irritation at the electrode contact site. Forexample, in one recent study of TTF therapy, forty-three percent (43%)of patients experienced some skin irritation, with 1% reporting severeskin irritation. The relatively high incidence of skin irritation orpain may prohibit the therapy in sensitive body areas (e.g., breasttissue, etc.). TTF therapy also involves the use of relatively highvoltages. For this reason, patients must be careful in performingeveryday activities having a risk of water exposure (e.g., showering,exercise (sweating), or even exposure to rain).

The use of electrodes in direct contact with the patient's skin presentsa risk of burning or heating of tissue adjacent to the electrodes.Because of this risk (and buildup of dirt, oils, etc.), the electrodesin TTF therapy systems typically require frequent replacement (e.g.,twice each week). Patients wearing TTF electrodes on the scalp reportedheadaches related to wearing the electrodes 24 hours a day.

TTF electrodes must also be placed by trained users (e.g., techniciansor physicians). Because the treatment is highly localized (i.e., betweenthe electrodes), precise location of the cancer/tumor must first beperformed, and the electrodes must be placed with a high degree ofaccuracy to create an electric field that passes through it. If theelectrodes are slightly off of optimal placement, the treatment mayresult in suboptimal results.

In addition, although the '289 patent discloses ambulatory embodiments(i.e., embodiments in which the patent can wear and use the system inperforming at least some ordinary non-stationary life activities such aswalking, driving, shopping, etc.), in practice the power requirements(e.g., high voltages) for generating appropriate electric fields (e.g.,at least 10 V/m) result in bulky and/or heavy electronics boxes thatmust be coupled to the electrodes and thus carried by the patient. Oneclinical study showed a relatively high rate of falls in patientscarrying these cumbersome TTF electronics boxes.

In view of these limitations to TTF systems, there is a need for safertherapies that may be applied for longer durations to destroy cancer orother rapidly-dividing cells. The many problems associated withelectrodes also raise a need for new therapies that avoid a risk of skinpain or the need for continuous contact with skin or other tissue.Because the efficacy of the system depends upon how long the electricfields can be applied to the rapidly-dividing cancer cells, less bulky,heavy, and cumbersome systems are needed to permit truly ambulatory,long duration treatments. Finally, there is a need for therapy systemsthat do not require trained patients or clinicians for setup.

SUMMARY

In one aspect, the present invention provides a method of treatingcancer cells in a target body area of a patient's body comprising:coupling a magnetic field generator to the target body area of thepatient's body; and applying an alternating polarity (AP) magnetic fieldto the target body area using the magnetic field generator, the APmagnetic field having a frequency of 0.5-500 kHz and a magnetic fieldstrength of 0.05-5 milliTesla (mT), wherein the AP magnetic fieldselectively affects the cancer cells to achieve at least one of damagingthe cancer cells, inhibiting the growth of the cancer cells, reducingtumor size, inhibiting angiogenesis, or preventing metastasis of thecancer cells, while leaving non-cancer cells substantially unharmed.

In another aspect, the present invention provides a system for treatingcancer cells in a target body area of a patient's body comprising: atleast one alternating polarity (AP) electromagnetic coil coupled to atarget body area of the patient's body; a power supply for supplyingpower to said at least one AP electromagnetic coil; and a controller forcontrolling the at least one AP electromagnetic coil and power supply togenerate and apply to the target body area an AP magnetic field having afrequency of 0.5-500 kHz and a field strength of 0.05-5 mT, wherein theAP magnetic field selectively affects the cancer cells to achieve atleast one of damaging the cancer cells, inhibiting the growth of thecancer cells, reducing tumor size, inhibiting angiogenesis, orpreventing metastasis of the cancer cells, while leaving non-cancercells substantially unharmed.

In another aspect, the present invention provides a system for treatingcancer cells in a target body area of a patient's body comprising: atleast one alternating polarity (AP) electromagnetic coil coupled to atarget body area of the patient's body; a retaining element to which theat least one AP electromagnetic coil is coupled, wherein the retainingelement is adapted to maintain the at least one AP electromagnetic coilin a desired position relative to the target body area; a power supplyfor supplying power to said at least one AP electromagnetic coil; and acontroller for controlling the at least one AP electromagnetic coil andpower supply to generate and apply to the target body area an APmagnetic field having a frequency of 0.5-500 kHz and a field strength of0.05-5 mT, wherein the AP magnetic field selectively affects the cancercells to achieve at least one of damaging the cancer cells, inhibitingthe growth of the cancer cells, reducing tumor size, inhibitingangiogenesis, or preventing metastasis of the cancer cells, whileleaving non-cancer cells substantially unharmed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic block diagram of a system for providing analternating polarity (AP) magnetic field to a target body area of apatient's body, according to one embodiment for selectively destroyingcells.

FIG. 2 is a front view of a retaining element comprising a bra havingone or more AP electromagnetic coils for providing an AP magnetic fieldto breast tissue, according to one embodiment of the invention.

FIG. 3 is a front view of a retaining element comprising a hat includingone or more AP electromagnetic coils for providing an AP magnetic fieldto brain tissue, according to one embodiment of the invention.

FIG. 4 is a front view of a retaining element comprising a shirt havingone or more AP electromagnetic coils for providing an AP magnetic fieldto thoracic or abdominal tissue, according to one embodiment of theinvention.

FIG. 5 is a front view of a retaining element comprising a neck cuff orcollar having one or more AP electromagnetic coils for providing an APmagnetic field to a target area of a patient's body, according to oneembodiment of the invention.

FIG. 6 is a front view of a retaining element comprising a bandagehaving one or more AP electromagnetic coils for providing an AP magneticfield to a target area of a patient's body, according to one embodimentof the invention.

FIG. 7A is a photograph at 10× magnification of untreated B16F10 mousemelanoma cells incubated for 24 hours.

FIG. 7B is a photograph of B16F10 mouse melanoma cells exposed to an APmagnetic field for 24 hours according to one embodiment of theinvention.

FIG. 8 is a bar graph showing the reduction in cell counts of B16F10mouse melanoma cells treated with an AP magnetic field for 24 hourscompared to untreated controls.

DESCRIPTION

Exemplary embodiments of the present disclosure are illustrated in thedrawings, which are illustrative rather than restrictive. No limitationon the scope of the technology or on the claims that follow is to beimplied or inferred from the examples shown in the drawings anddiscussed here.

In some embodiments, the invention provides apparatus and methods fortreating a patient having cancer or other rapidly dividing cells (e.g.,bacterial infection) in a target body area using alternating polarity(AP) magnetic fields at specified frequencies to destroy or inhibit theproliferation of the rapidly dividing cells. The use of electric fields,including without limitation TTF systems, to treat patients havingcancer or other diseases characterized by rapidly-dividing cells has anumber of limitations that make treatment for some patients difficult,ineffective, painful, or unsafe. Embodiments of the present inventionovercome one or more of these limitations by using AP magnetic fields totreat rapidly-dividing or hyperproliferating cells.

As used herein, the terms “magnetic field tumor (MFT) therapy” and“MFTT” refer to systems and methods for treating cancer or otherrapidly-dividing cells with AP magnetic fields at specified frequenciesand magnetic field strengths to destroy or inhibit the proliferation ofsuch cells. In various embodiments, the present invention may be used totreat one or more cancers such as throat cancer, thyroid cancer, mouthcancer, nose cancer, salivary gland cancer, lung cancer, lung carcinoidtumors, thymic malignancies, tracheal tumors, pancreatic cancer, livercancer, stomach cancer, kidney cancer, ovarian cancer, prostate cancer,colon cancer and rectal cancer.

FIG. 1 is a simplified schematic block diagram illustrating certaincomponents of an MFT therapy system 100 according to an embodiment ofthe invention. The MFT therapy system 100 includes an alternatingpolarity magnetic field generator (APMFG) 110 to generate an electricalsignal to energize one or more alternating polarity (AP) electromagneticcoils 120 to produce an AP magnetic field having specified frequency andfield strength characteristics. In one embodiment, the APelectromagnetic coils 120 may have sizes and shapes adapted to engageone or more target body areas of a patient (e.g., torso, breast, head,neck, throat) for treatment of cancer or hyperproliferating cells in thetarget body area. The electrical signals generated by APMFG 110 andapplied to AP electromagnetic coils 120 is controlled by a controller130, which specifies the parameters of the magnetic fields to begenerated by APMFG 110 and AP electromagnetic coils 120, and controlsthe function and operation of the system 100. An interface 140 isprovided to allow a user to specify treatment parameters to beprogrammed or communicated to the controller 130, and to receiveinformation from the controller relating to the operation and status ofthe MFT therapy system 100. A power supply 150 provides power to MFTtherapy system 100. Power supply 150 may be selected from a variety ofknown power supplies, and may comprise, in various embodiments, abattery such as a disposable or rechargeable battery, or a power sourcesuch as a standard 120V, 60 Hz electrical power outlet in the US,together with circuitry for regulating the power at appropriate currentsand voltages for each of the APMFG 110, AP electromagnetic coils 120,controller 130, and interface 140.

Controller 130 may include circuitry and other components (e.g.,microcontrollers, resistors, registers, memory, firmware, software,etc.) to direct and control the operations of the APMFG 110, APelectromagnetic coils 120, and interface 140. FIG. 1 illustrates anembodiment in which the AP electromagnetic coils 120 are energizeddirectly from the magnetic field generator. In an alternative embodiment(not shown), controller 130 may communicate directly with each of theone or more AP electromagnetic coils 120 to control their operation inwhole or in part (e.g., by switches that enable or disable each APelectromagnetic coil 120).

Controller 130 includes a timing control module 112 for controlling thetiming of the MFT therapy delivered by AP electromagnetic coil(s) 120 toone or more target body areas or tissues. In various embodiments, timingcontrol module 112 may cause the AP magnetic field generator 110 and APelectromagnetic coils 120 to provide MFT therapy for a programmedduration such as 1-100 hours or other treatment period, or the timing ofand between a plurality of therapy treatment periods. For example, thetiming control module 112 may implement a first therapy for a first timeperiod (e.g., during waking hours of the patient) at a first frequencyand field strength, followed by a second time period in which no therapyis applied, followed by a third time period in which a second therapy isimplemented at a second frequency and second field strength. Timingcontrol module 112 may also control the timing of changes in othertreatment parameters, such as changes in the frequency or field strengthof the MFT therapy applied to the patient.

A frequency control module 114 controls the frequency of the AP magneticfields delivered by AP electromagnetic coil(s) 120 to the one or moretarget body areas or tissues. Frequency control module 114 may controlthe frequency of the AP magnetic field at a programmed frequency of0.5-500 kHz. In some embodiments, the frequency control module 114 maycontrol frequency changes to the AP magnetic fields generated by theAPMFG 110 and the AP electromagnetic coils 120 at a programmed rate ofchange or according to specific frequency step changes.

A magnetic field strength control module 116 controls the field strengthof the AP magnetic fields applied to the one or more target body areas.Magnetic field strength control module 116 may control the fieldstrength ata programmed magnetic field strength of 0.05-5 mT, and maycontrol changes in the field strength according to a programmed rate ofchange or programmed step changes in field strength.

Controller 130 may include programming logic, timers, and othercircuitry to accomplish the functions of the timing control module 112,frequency control module 114, and magnetic field strength control module116. It will be appreciated in alternative embodiments, the functions ofall or portions of timing control module 112, frequency control module114, and magnetic field strength control module 116 may be combined intoone or more submodules, or implemented by controller 130 as a whole.

In one embodiment, interface 140 may include a user input, such as akeyboard or buttons, to allow a user to input or receive data fromcontroller 130. In a further embodiment (not shown,) interface 140 maybe located within controller 130 and may comprise a transceiver tocommunicate with a separate user device (not shown) such as a cellphone, tablet, or other computing device to program the MFT therapysystem 100 and receive data therefrom (e.g., operating and alarm statusflags, programmed parameters, treatment time, etc.). In otheralternative embodiments (not shown), interface 140 may be omitted, ormay be incorporated as part of a single unit having some or all of thefunctions of AP magnetic field generator 110, controller 130, andinterface 140.

Referring again to FIG. 1 , in various embodiments the APMFG 110 mayprovide an electrical signal to cause each of the one or more APelectromagnetic coils 120 to generate magnetic fields having one or morefixed or variable AP frequencies. Although shown in the simplifiedschematic diagram of FIG. 1 as coupled to APMFG 110 by a single wire, itwill be understood that each of AP electromagnetic coils 120 willgenerally be coupled to APMFG 110 by a pair of wires (not shown) toprovide a complete circuit. In fixed-frequency embodiments, APMFG 110may cause each of the one or more AP electromagnetic coils 120 togenerate a magnetic field having a single frequency or a plurality offrequencies either continuously or intermittently according to a definedduty cycle (e.g., having a programmable on-time during which themagnetic field is emitted from AP electromagnetic coils 120, followed byan off-time during which no field is emitted). The APMFG 110 may alsocause the one or more AP electromagnetic coils 120 to generate APmagnetic fields having a variety of waveforms, e.g., sinusoidal,triangular, trapezoidal etc. In some embodiments the APMFG 110 may causethe one or more AP electromagnetic coils 120 to generate AP magneticfields having a pre-defined number of waveforms of a specified firstfrequency, and repeat this pattern at a second specified frequency(burst mode). In other embodiments, the APMFG 100 may cause the one ormore AP electromagnetic coils 120 to generate a magnetic field having awaveform which uses a fixed frequency or a combination of frequenciescoupled with amplitude modulation.

Whether fixed or variable, the frequency (or frequencies) of the APmagnetic fields generated by each AP electromagnetic coil 120 arepreferably frequencies below about 1 MHz, and more preferably arefrequencies within the range of 0.5-500 kHz, more preferably within therange of 25-400 kHz, and still more preferably within the range of100-300 kHz. In one embodiment, the MFT therapy system 100 may compriseat least two AP electromagnetic coils 120, each having a fixed orvariable frequency within a different frequency range to providemagnetic fields at multiple frequencies to a target body area or tissue.For example, APMFT 110 may generate a first electrical signal to cause afirst AP electromagnetic coil 120 to generate an AP magnetic field witha first fixed frequency or a variable first frequency within a firstfrequency range, and a second electrical signal to cause a second APelectromagnetic coil 120 to generate an AP magnetic field with a secondfixed frequency or a variable second frequency within a second frequencyrange, where both the first frequency range and the second frequencyrange are ranges within the range of 0.5-500 kHz. As a nonlimitingexample, the first range may be a low-frequency range (e.g., 1-5 kHz)and the second frequency range may be a higher-frequency range (e.g., 50kHz-300 kHz).

Without being bound by theory, it is believed that AP magnetic fieldswithin a plurality of frequency sub-ranges within the range of 0.5-500kHz may affect different aspects of the reproduction cycle ofrapidly-dividing cells, and that each such aspect may be more stronglyaffected by AP magnetic fields within a particular frequency sub-rangewithin the broader range of 0.5-500 kHz. For example, the interruptionof angiogenesis by extremely low frequency AP magnetic fields has beenreported for AP magnetic fields having a frequency of 50 Hz (Monache etal., “Inhibition of Angiogenesis Mediate by Extremely Low-FrequencyMagnetic Fields (ELF-MFs),” PLOS One, 8:11 (November 2013). Differenttypes of cells, including without limitation different types of cancercells, may require different frequencies for interruption ofangiogenesis.

Accordingly, in one embodiment an MFT therapy having a bimodal magneticfield frequency distribution may be applied to the target body area. Inone exemplary embodiment, the APMFT 110 may generate a first electricalsignal to cause a first AP electromagnetic coil 120 to generate a firstvariable AP magnetic field distribution that varies the magnetic fieldfrequency over a first time period (e.g., 1 second, 1 minute, 10minutes, 1 hr) between a first lower limit (e.g., 0.5 kHz) and a firstupper limit (e.g., 5 kHz) to broadly interrupt a first metabolic process(e.g., angiogenesis) in a target cell population, as defined byfrequency control module 114. The APMFT 110 may also generate a secondelectrical signal to cause the same or a second AP electromagnetic coil120 to generate a second variable AP magnetic field distribution thatvaries the magnetic field frequency over a second time period (e.g., 1second, 1 minute, 10 minutes, 1 hr) between a second lower limit (e.g.,50 kHz) and a second upper limit (e.g., 400 kHz) to broadly interrupt asecond metabolic process (e.g., the mitosis cycle) of rapidly-dividingcells. Additional coils may produce different fixed orvariable-frequency AP magnetic fields having different frequencies orfrequency ranges to interrupt still other aspects of the reproductioncycle of rapidly-dividing cells. In an alternative example, a single APelectromagnetic coil 120 may be used to sequentially deliver AP magneticfields within two different AP frequency ranges (e.g., 1-5 kHz for afirst treatment period, followed by 50-400 kHz for a second treatmentperiod).

In variable-frequency embodiments, many different ways of implementing achanging frequency are possible, and enumeration herein of specificembodiments of varying frequencies is illustrative and is not intendedto be limiting. It will be appreciated that additionalvariable-frequency embodiments may be implemented in view of the presentdisclosure. In one embodiment, a magnetic field may be generated havinga single frequency that varies from a lower frequency (e.g., 50 kHz) toan upper frequency (e.g., 250 kHz) in a uniform manner (i.e.,non-varying rate of frequency change) within a defined frequency rangetime period or at a desired (e.g., programmed) frequency change rate. Inanother embodiment, the frequency may vary in a non-uniform manner suchas stepwise changes in frequency or different rates of change (e.g.,rates of change of frequency are highest near the mid-point between theupper and lower frequency limits). In a still further embodiment, thefrequency may vary continuously or intermittently, withvariable-frequency periods alternating with non-variable frequencyperiods. In additional embodiments, a field having two differentfrequencies may simultaneously be applied to the target body area(emitted, e.g., by a single coil or by two different coils). Byproviding multiple (e.g., 2 or more) coils, MFT therapies having adesired frequency distribution (e.g., random, Gaussian, or non-Gaussian)either sequentially or simultaneously may be applied to one or moretarget areas.

The electrical signal from APMFG 110 to AP electromagnetic coils 120also defines the field strength of the AP magnetic fields produced bythe coils, as defined by magnetic field strength control module 116. MFTtherapy systems 100 of the present invention may use relatively lowmagnetic field strengths to destroy or impair rapidly-proliferatingcells. Preferably, MFT therapy fields in systems 100 of the presentinvention have field strengths of less than 5 milliTesla (i.e., 5,000μT), such as field strengths within the range of 0.05-5 mT. In apreferred embodiment, the field strengths are within the range of 0.2-2mT, and more preferably within the range of 0.5-1.2 mT.

In one embodiment, the magnetic field may have a single, non-varyingfield strength. Without being bound by theory, it is believed thatdifferent cell sizes (e.g., different types of cancers) may requiredifferent field strengths for maximum efficacy in destroying orinhibiting cell division. Within such embodiments, however, the APmagnetic fields may have a single, non-varying field strength eithercontinuously or intermittently according to a defined duty cycle asdefined by, e.g., timing control module 112 and magnetic field strengthcontrol module 116.

In variable-field-strength embodiments, many different ways of varyingthe field strength can be envisioned, similar to the variationsdescribed above respecting frequency changes. As with frequency,enumeration herein of specific embodiments of varying field strength isillustrative, not limiting. Additional variable-field-strengthembodiments may be implemented (e.g., by magnetic field strength controlmodule 116) in view of this disclosure. In one embodiment, a magneticfield may have a field strength that varies from a lower limit (e.g.,0.05 mT) to an upper limit (e.g., 1 mT) in a uniform manner (i.e., witha non-varying rate of change) within a defined field strength range timeperiod. In another embodiment, the field strength may vary in anon-uniform manner such as stepwise changes in field strength or with aswept field strength variation with accelerating or decelerating fieldstrength variation (e.g., rates of change of field strength are highestnear the upper and lower limits of the field strength range). In a stillfurther embodiment, magnetic field strength may vary continuously orintermittently, with variable-field-strength periods alternating withnon-variable-field-strength periods. In some embodiments, AP magneticfields at two different frequencies, each having a different fieldstrength, may simultaneously be applied to the target body area(emitted, e.g., by two different AP electromagnetic coils 120). Byproviding multiple AP electromagnetic coils 120, MFT therapies having adesired frequency and magnetic field strength distribution (e.g.,random, Gaussian, or non-Gaussian), either sequentially orsimultaneously may be applied to the target body area.

Because MFT therapies act only on dividing cells, overall efficacycorresponds to lengthy treatment periods (e.g., many hours or days, andin some cases weeks). However, to minimize damage to normal (e.g.,non-cancerous or non-tumor) cells, in some embodiments the therapy issuspended for certain periods. This may involve, for example, providingMFT therapy continuously with defined alternating on-time (e.g., a timeperiod withing a range of 1 sec-24 hr) and off-time (e.g., 1 sec-24 hr)periods according to a defined treatment duty cycle as defined by timingcontrol module 112. In one embodiment, the on-time and off-time periodsmay be a time period within a range of 1 second-1 week, 1 sec-24 hr, 1minute-12 hr, etc.). In one such exemplary embodiment, the MFT therapyis provided continuously at a 10:1 duty cycle by generating and applyingthe MFT therapy fields for ten (10) minutes, followed by 1 minute inwhich no therapy is applied, with the process repeated until apredefined total treatment duration (e.g., 2 weeks) is complete. Inanother embodiment, the same 10:1 duty cycle may be administered byapplying the MFT therapy fields for ten hours, followed by a one-hoursuspension of therapy, and repeating the process until the totaltreatment period is complete.

In another embodiment, MFT therapy according to a defined treatment dutycycle comprising on-time and off-time periods may be administered for adefined treatment duration (e.g., 1 hr, 6 hr, 8 hr, 24 hr) after whichno further treatment is applied. In a still further embodiment, the MFTtherapy may be administered according to the patient's circadian rhythms(e.g., continuously at night or when the patient is sleeping, andaccording to a defined duty cycle for defined periods during the daysuch as morning hours, afternoon hours, or evening hours). It will beappreciated that other duty cycles and treatment durations may be used,and that the therapy may involve, as previously discussed, constant orvariable magnetic field frequencies and field strengths.

In another embodiment, MFT therapy may be applied according to a definedtreatment duty cycle of on-time and off-time periods, with the magneticfield strength varying according to a defined field strength duty cycle.This may involve, for example, a 10:1 treatment duty cycle combined witha 4:1 field strength duty cycle. As a specific example, the MFT therapymay be provided for a 24 hr treatment duration, at a 10:1 treatment dutycycle with AP magnetic fields applied to a target body area for 10minutes, followed by 1 minute in which no AP magnetic fields areapplied. Within the 10 minute treatment periods, 8 minutes may involvevariable frequency treatment within a first field strength range of3.0-4.0 mT, followed by 2 minutes of treatment within a second fieldstrength range of 0.5-1.5 mT, providing a 4:1 field strength duty cycle.

In alternative embodiments, MFT therapy fields may be applied accordingto the patient's circadian rhythms, or according to specific times ofday. For example, the MFT therapy fields may be applied to the targetbody area only during daytime hours; only during nighttime hours; duringall daytime hours except during mealtime hours; during all daytime hoursexcept when the patient is exercising (as detected by, e.g., an activitymonitor); during specific hours of the day (e.g., 9:00 AM-noon and 6:00PM-5:00 AM). These examples are intended to be exemplary only, and itwill readily be appreciated that delivery of MFT therapy fields can betailored to suspend therapy during certain hours that would be mostconvenient to the patient, while also minimizing damage to normal (i.e.,non-rapidly-dividing) cells.

Most magnetic field-generating coils are constructed so as to generate amagnetic field having an axis along which the magnetic field lines aredirected. In some embodiments, multiple AP magnetic coils 120 can bespatially aligned in such a manner that a desired magnetic fielddistribution is generated in area of interest, such as the entirety or aportion of the target body area.

In some embodiments, one or more parameters defining the MFT therapy(e.g., frequency, field strength, selection of specific coils among aplurality of available coils) may be determined based on the results ofcertain tests. For example, an imaging procedure may be performed toidentify the type and location of the target rapidly-dividing cells(e.g., cancer or tumor cells). In various embodiments, the imagingprocedure may be an imaging procedure using one or more of an MRIsystem, a CT scan system, a PET scan system, and an X-ray system.

Based on the results of the imaging (e.g., cell size(s), type of cells,location of cells, etc.) a healthcare provider such as a physician mayselect one or more parameters of the MFT therapy, including withoutlimitation, the frequency/frequencies of the magnetic field(s), thefield strength(s), the positioning of one or more coils, a coil size, atype of retaining element (e.g., a garment type) to maintain the coilsin position relative to the target body area, a duty cycle or schedulefor applying therapy, etc. It will be appreciated that the foregoing andother parameters may also be selected based on other tests, e.g., apathological analysis of the cancer cells such as a microscopic analysisof a biopsy, a chemical test, a genetic test, etc.

In some instances, the results of an imaging procedure prior to the MFTtherapy may identify a target body area to which MFTT is to be directed.Based on the location of the target body area, in some embodiments aretaining element may be necessary to retain the magnetic coils in adesired position relative to the target treatment area or tissue.Various retaining elements may be used to unobtrusively and securelymaintain the magnetic coils in a desired position relative to a desiredtarget area of the patient's body. For example, a bra may be used tohouse the magnetic coils for treatment of breast cancer cells. Inanother example, a hat may be used to retain magnetic coils in positionto treat brain cancer. In still another example, a neck cuff, collar, orscarf may retain one or more magnetic coils for treatment of esophagealcancer, and a shirt may be used to retain one or more magnetic coils totreat lung cancer. In another embodiment, the retaining element may be abandage such as an adhesive bandage capable of adhering to the targetbody area or to skin adjacent thereto. These examples are exemplary andnot limiting, and it will be appreciated that a variety of other oradditional retaining elements may be used depending upon the targettissue location. Because the magnetic coils do not need to be in directcontact with the skin of the patent, the retaining elements may includepouches or pockets for securely retaining the coils in position with acomfortable and biocompatible lining placed between the coil and theskin or target treatment area. In some embodiments, the APelectromagnetic coils 120 are completely integrated within the retainingelement during manufacturing (e.g., the coils are completely integratedinside a garment such as a bra, hat, shirt, bandage, etc.) In variousembodiments, the retaining element may include a lead wire for couplingeach of the one or more coils 120 to the AP magnetic field generator 110and/or controller 130. In alternative embodiments, a direct electricalcoupling (e.g., a snap fit) may be used between an electronics packageand the AP electromagnetic coil(s) 120. The electronics package mayinclude one or more of the power supply 150, controller 130, APMFG 110,and interface 140.

FIG. 2 illustrates a bra 200 that acts as a retaining element for one ormore magnetic coils 220 for applying one or more magnetic fields to atarget body area to treat cancer cells or other rapidly-dividing cellsin breast tissue. Magnetic coils 220 may be the same as coils 120described in FIG. 1 , but may be adapted for placement in bra 200 (e.g.,with a size, geometry, etc., for treatment of breast tissue). Bra 200may in many aspects be constructed similarly to existing bras availableat retail clothing outlets, and may include cups 210 for holding breasttissue and retaining coils 220 in position relative to a target bodyarea comprising breast tissue. Straps 230 may be provided to secure thebra 200 to the shoulders of the patient, and side straps or bands 240for securing the bra to the patient's torso. AP electromagnetic coils220 may be integrated into bra 200, or may be removably coupled thereto.

One or more cables or wires 250 may be provided to couple each of thecoils 220 to an electronics box 260, which may house the remainingcomponents of the MFT therapy system 100 of FIG. 1 such as APMFG 110,controller 130, power supply 150, and in some embodiments interface 140.In alternative embodiments, one or more of the APMFG 110, controller130, power supply 150, or interface 140 may be provided separately fromthe electronics box 260. For example, interface 140 may comprise amobile phone app that communicates directly with one or more of APMFG110, controller 130, power supply 150, etc., as well as receiving anddisplaying information from one or more of the foregoing systemcomponents. The mobile phone app interface may allow the patient or ahealthcare provider to program one or more treatment parameters for theMFT therapy system 100, and may display information relating to the MFTtherapy or system 100 status (e.g., displaying how long the MFT therapyhas been applied, whether a magnetic field is currently being applied tothe target tissue from each of the coils 220, the frequency and/or fieldstrength of the currently-provided magnetic fields, remaining batterylife, etc.).

FIG. 3 illustrates a hat 300 that acts as a retaining element for one ormore AP electromagnetic coils 320 for applying one or more magneticfields to the treatment of cancer or other rapidly-dividing cells in atarget body area comprising brain tissue. Magnetic coils 320 are, in oneembodiment, similar to AP electromagnetic coils 120 described in FIG. 1, but may be adapted for placement in hat 300. This may include changesin the size, geometry, or other characteristics to enable effectiveplacement in hat 300 for treatment of brain tissue. Although depicted asa baseball cap, it will be apparent that many other hat types and stylesmay be used for hat 300 (e.g., skullcap, beret, fedora, etc.). In oneembodiment, hat 300 may be a skullcap of an appropriate size to fitclosely on the head of the patient, and the magnetic coils 320 may havea concave shape adapted for location or placement in the cap, e.g.,inside the hat or in a pocket between an inner and outer layer thereof.AP electromagnetic coils 320 may be integrated into hat 300, or may beremovably coupled thereto.

One or more cables or wires 350 may be provided to couple each of the APcoils 320 to an electronics box 360, which may house the remainingcomponents of the MFT therapy system 100 of FIG. 1 such as APMFG 110,controller 130, power supply 150, and in some embodiments interface 140.In alternative embodiments, one or more of the APMFG 110, controller130, power supply 150, or interface 140 may be provided separately fromthe electronics box 360. For example, as described in connection withFIG. 2 , a separate interface 140 may be provided as a mobile phone appthat communicates directly with one or more of APMFG 110, controller130, power supply 150, etc. Such an app-based interface may also provideinformation on the MFT therapy to the patient or a healthcare provider(e.g., displaying how long the MFT therapy has been applied, whether amagnetic field is currently being applied to the target tissue from eachof the coils 320, the frequency and/or field strength of thecurrently-provided magnetic fields, remaining battery life, etc.).

FIG. 4 illustrates a shirt 400 that acts as a retaining element for oneor more AP electromagnetic coils 420 for applying one or more magneticfields to the treatment of cancer or other rapidly-dividing cells in atarget tissue in a patient's thoracic or abdominal region. This mayinclude, without limitation and depending on the placement of the one ormore AP electromagnetic coils 420, treatment of lung cancer, livercancer, pancreatic cancer, or cancers or tumors in other thoracic orabdominal organs or structures. AP electromagnetic coils 420 are, in oneembodiment, similar to coils 120 described in FIG. 1 , but may beadapted for placement in shirt 400 based on the target tissue. This mayinclude changes in the coil size, geometry, or other characteristics toenable effective placement in shirt 400 and for treatment of theparticular target tissue. Although depicted as a T-shirt, that manyother types and styles of shirt may be used as shirt 400, includinglong-sleeve or short sleeve shirts; button, zip, or pullover shirts. Inaddition, it will be understood that shirt 400 may comprise othergarments that may cover the thoracic or abdominal region of a patient,including sweaters, jackets, coats, etc., although in preferredembodiments a shirt that fits tightly to the patient's body is used tobetter retain the AP electromagnetic coils 420 in a more precise orcontrolled placement relative to the target tissue. AP electromagneticcoils 420 may be adapted for location or placement on the inside,outside or in a pocket of shirt 400, and may be integrated into orremovably coupled thereto.

One or more cables or wires 450 may be provided to couple each of thecoils 420 to an electronics box 460, which may house the remainingcomponents of the MFT therapy system 100 of FIG. 1 such as APMFG 110,controller 130, power supply 150, and in some embodiments interface 140.In alternative embodiments, one or more of the APMFG 110, controller130, power supply 150, or interface 140 may be provided separately fromthe electronics box 460. For example, a separate interface 140 may beprovided as a mobile phone app that communicates with one or more ofAPMFG 110, controller 130, power supply 150, etc. Such an app-basedinterface may also provide information on the treatment therapy to thepatient or a healthcare provider (e.g., displaying how long the therapyhas been applied, whether a magnetic field is currently being applied tothe target tissue from each of the coils 420, the frequency and/or fieldstrength of the currently-provided magnetic fields, remaining batterylife, etc.).

FIG. 5 illustrates a neck cuff or collar 500 that acts as a retainingelement for one or more AP electromagnetic coils 520 for applying one ormore magnetic fields to the treatment of cancer or otherrapidly-dividing cells in a target tissue in a patient's neck area,including without limitation esophageal cancer, laryngeal cancer, etc.AP electromagnetic coils 520 may be similar to coils 120 described inFIG. 1 , but may be adapted for placement in neck cuff or collar 500based on the target treatment area or tissue. This may include changesin the size, geometry, or other characteristics to enable effectiveplacement in neck cuff 500 and for treatment of the particular targettissue. Neck cuff or collar 500 preferably includes a securing and/oradjustment tab 530 (e.g., Velcro) to adjust the cuff or collar to thepatient's size and to secure it in a fixed position relative to thepatient's neck. In one alternative embodiment, a neck scarf may be usedas a retaining element. AP electromagnetic coils 520 may be adapted forlocation or placement on the inside, outside or in a pocket of neck cuffor collar 500, and may be integrated into or removably coupled thereto.

One or more cables or wires 550 may be provided to couple each of thecoils 520 to an electronics box 560, which may house the remainingcomponents of the MFT therapy system 100 of FIG. 1 such as APMFG 110,controller 130, power supply 150, and in some embodiments interface 140.In alternative embodiments, one or more of the APMFG 110, controller130, power supply 150, or interface 140 may be provided separately fromthe electronics box 560. For example, a separate interface may beprovided as a mobile phone app that communicates with one or more ofAPMFG 110, controller 130, power supply 150, etc. Such an app-basedinterface may also provide information on the treatment therapy to thepatient or a healthcare provider (e.g., displaying how long the therapyhas been applied, whether a magnetic field is currently being applied tothe target tissue from each of the coils 520, the frequency and/or fieldstrength of the currently-provided magnetic fields, remaining batterylife, etc.).

FIG. 6 illustrates a bandage 600 that acts as a retaining element forone or more magnetic coils 620 for applying one or more magnetic fieldsto the treatment of cancer or other rapidly-dividing cells in a targettissue anywhere on the body. Magnetic coils 620 may be similar to thosedescribed in FIG. 1 , but may be adapted for placement in bandage 600based on the target tissue. This may include changes in the size,geometry, or other characteristics to enable effective placement inbandage 600 and for treatment of any of a variety of different targettissues. Magnetic coils 620 may be adapted for location or placement onthe inside, outside or in a pocket of bandage 600, and may be integratedinto or removably coupled thereto.

One or more cables or wires 650 may be provided to couple each of thecoils 620 to an electronics box 660, which may house the remainingcomponents of the MFT therapy system 100 of FIG. 1 such as APMFG 110,controller 130, power supply 150, and in some embodiments interface 140.In alternative embodiments, one or more of the APMFG 110, controller130, power supply 150, or interface 140 may be provided separately fromthe electronics box 560. For example, a separate interface may beprovided as a mobile phone app that communicates with one or more ofAPMFG 110, controller 130, power supply 150, etc. Such an app-basedinterface may also provide information on the treatment therapy to thepatient or a healthcare provider (e.g., displaying how long the therapyhas been applied, whether a magnetic field is currently being applied tothe target tissue from each of the coils 620, the frequency and/or fieldstrength of the currently-provided magnetic fields, remaining batterylife, etc.).

Certain embodiments of the retaining element may also provide additionalfeatures to enable the MFT therapy to be conveniently delivered to thetarget body area or tissue. In one embodiment, the retaining element mayhave integrated magnetic coils 120, APMFG 110, and controller 130,either as separate items in the retaining element or as a single unit. Awire (not shown) may be provided to couple the power supply to one ormore of the APMFG 110, coils 120, controller 130, and interface 140. Inone embodiment, the power supply 150 provides power to the controller,which includes circuitry (e.g., rectifiers, converters, transformers,etc.) to modify the electrical power received from the power supply toprovide electrical power to controller 130, which in turn distributespower to the APMFG 110, AP electromagnetic coils 120, and interface 140.In this embodiment, a power supply (e.g., a battery) may be locatedelsewhere in close proximity to the patient (e.g., in a pocket in thepatient's trousers or a jacket).

In some embodiments, the MFT therapy may be provided to a patient incombination with one or more other therapies such as an anti-cancerdrug, radiation therapy, or TTF therapy (e.g., therapy as described inU.S. Pat. No. 6,868,289 or U.S. Pat. No. 8,019,414). The MFT therapysystem 100 preferably permits the other (i.e., non-MFT) therapy to beprovided at a lower dosage than would be administered in the absence ofthe MFT therapy to the target body area or tissue, or at a reducedfrequency than would be administered in the absence of the MFT therapy,or both. In various embodiments, the co-therapy applied with the MFTtherapy may be a drug selected from a chemotherapy drug, a hormonereceptor drug, targeted therapy drugs, immunotherapy, angiogenesisinhibitor drugs, a checkpoint inhibitor drug, and a HER2 receptor drug.In other embodiments the co-therapy may be a radiation therapy selectedfrom an internal radiation therapy and an external beam radiationtherapy. In still other embodiments, the co-therapy applied with the MFTtherapy may be a TTF therapy involving the application of electricalfields to the target tissue. Without being bound by theory, it isanticipated that one or more co-therapies (or adjuvant therapies), whencombined with MFT therapy, may achieve superior results than eithertherapy when administered alone. In various embodiments, the combinationtherapy may comprise administering MFT therapy with an anti-cancer drug,radiation, or TTF therapy either simultaneously or sequentially.

It may be desirable in some instances to shield non-target body areasfrom the MFT therapy fields. In such instances an optional magneticfield shield (not shown) may be provided to shield the non-target areasfrom the effects of the magnetic fields. In some embodiments, highlylocalized shields may be provided to shield specific structures withinthe target body area of the patient, such as specific blood vessels ororgan structures that are adjacent to the target rapidly-dividing cells.

It is known that electric fields induce magnetic fields and vice versa.However, without being bound by theory, the present invention involvingMFT therapy appears to provide a therapy having a different mode ofaction than prior art TTF and/or drug therapies. In particular, TTFtherapies use capacitive electrodes to induce primarily electric fieldsat relatively high electric field strengths. According to reportedliterature (e.g., Kirson et al., Cancer Research 2004) TTF therapiesbegin to inhibit tumor cell growth at a field strength of about 100 V/mat frequencies of 50-250 kHz. In one recent experiment (see Experiment 1below), MFT therapies showed surprising results with a similarinhibition of tumor cell growth as reported for TTF therapies but at afraction (e.g., less than 3%) of typical TTF therapy electric fieldstrengths.

EXPERIMENT 1

Mouse melanoma cells (B16F10 cell line, obtained from the University ofCalifornia-Berkeley) were incubated in Dulbecco's Modified Eagle Medium(DMEM) in 36 middle wells (5.0 mm diameter) of a 96 well plate for 24hours at 37° C. The cells in each of the 36 treatment wells were thenexposed for 24 hours to an alternating magnetic field at a frequency of150 kHz and a magnetic field strength of approximately 0.8 mT using aHelmholtz coil, maintained at a temperature of 37° C. Control wells werenot exposed to the alternating magnetic field and were incubated at 37°C. for the same time period. After 24 hours, the alternating magneticfield was discontinued and histology was performed for cells in eachwell (both treatment and control). FIGS. 7A and 7B are illustrative ofthe differences between typical control and treatment wells. Controlsexhibited a significantly higher cell count per well as shown by grosscomparison. In addition, control cells maintained a typically angularmorphological structure as indicating in FIG. 7A. Magnetic field-treatedcells showed significantly decreased cell count and in additiondemonstrated rounded morphology indicating cell stress, as shown in FIG.7B.

FIG. 8 provides a bar chart comparison summarizing the results oftreatments performed on two different plates with 36 wells in eachplate. Normalizing the cell counts of the control wells as 100, thetreated cells showed a reduction of approximately 31%. Althoughtreatment by magnetic fields and electrical fields (e.g., TTF therapy)are fundamentally different (e.g., using coils vs electrodes andgenerating primarily magnetic vs. electric fields), it is possible tocalculate the strength of the induced electric field from the coils usedin Experiment 1 using the equation

$E_{nc} = {\frac{r}{2}\frac{dB}{dt}}$

Using equation 1 yields a maximum inducted voltage of 2.34 V/m, or lessthan 3% of the electric field strengths reported as required forinhibitory activity in TTF therapy. Because Experiment 1 indicates thatMFT therapy exhibits effects on cancer cells at such a small fraction ofthe electrical field strength of TTF therapy, it enables therapieshaving significant advantages over TTF therapies, including withoutlimitation ambulatory therapies that allow patients to continue manyordinary day-to-day activities without interruption, and minimalencumbrance or burden.

Part of the advantage of MFT therapies over TTF therapies stems from thedifferent hardware configurations of the two systems. While TTFtherapies use insulated (e.g., ceramic coated) electrodes, the use ofcoils instead of electrodes in MFT therapy confers a number of benefits.Because MFT therapy coils-in contrast to the insulated electrodes of TTFtherapies-do not need to be in direct contact with the body, MFT coilscan be separated from target issue by one or more clothing layers (e.g.,a garment or undergarment). By applying magnetic fields throughclothing, MFT therapies provide increased patient comfort and a lesscumbersome patient experience.

In addition, MFT therapies can be implemented with significantly lessrisk to the patient than TTF therapies involving electrodes. The use ofcoils instead of electrodes results in only a de minimis inducedelectrical current during MFT therapies, and thus the risk of electricalshorting and consequent uncontrolled heating of patient body tissue isnegligible.

Furthermore, because MFT therapies involve coils that can be maderelatively small and with no current flow through the patient's body,systems for MFT therapies can allow long treatment periods to targetcancer and other hyperproliferating cells with little inconvenience tothe patient. These and other advantages of MFT therapies over TTFtherapies will be more fully appreciated by persons of skill in the artin view of the present disclosure.

In various embodiments, the present invention relates to the subjectmatter of the following numbered paragraphs.

101. A method of treating cancer cells in a target body area of apatient, com prising:

-   -   coupling an AP electromagnetic coil to the target body area; and    -   applying an alternating polarity (AP) magnetic field to the        target body area using the AP electromagnetic coil, the AP        magnetic field having a frequency of 0.5-500 kHz and a field        strength of 0.05-5 mT, wherein the AP magnetic field selectively        affects the cancer cells to achieve at least one of damaging the        cancer cells, inhibiting the growth of the cancer cells,        reducing tumor size, inhibiting angiogenesis, or preventing        metastasis of the cancer cells, while leaving non-cancer cells        substantially unharmed.

102. The method of numbered paragraph 101, further comprising:

-   -   coupling a controller to the AP electromagnetic coil, wherein        the controller controls the frequency and field strength of the        AP magnetic field.

103. The method of numbered paragraph 101, wherein applying an APmagnetic field comprises applying an AP magnetic field having afrequency of 25-400 kHz and a field strength of 0.2-2 mT.

104. The method of numbered paragraph 101, wherein applying an APmagnetic field comprises applying an AP magnetic field having afrequency of 100-300 kHz and a field strength of 0.5-1.2 mT.

201. A method of treating cancer cells in a target body area of apatient, comprising:

-   -   providing at least one electromagnetic coil;    -   providing a controller coupled to the at least one        electromagnetic coil;    -   coupling the at least one electromagnetic coil to the target        body area;    -   applying to the target body area an alternating polarity (AP)        magnetic field having a frequency of 0.5-500 kHz and a field        strength of 0.05-5 mT, wherein the AP magnetic field is        generated by the at least one electromagnetic coil under the        control of the controller, and the AP magnetic field selectively        affects the cancer cells to achieve at least one of damaging the        cancer cells, inhibiting the growth of the cancer cells,        reducing tumor size, inhibiting angiogenesis, or preventing        metastasis of the cancer cells, while leaving non-cancer cells        substantially unharmed.

202. The method of numbered paragraph 201, wherein applying an APmagnetic field comprises applying an AP magnetic field having afrequency of 25-400 kHz and a field strength of 0.2-2 mT.

203. The method of numbered paragraph 201, wherein applying an APmagnetic field comprises applying an AP magnetic field having afrequency of 100-300 kHz and a field strength of 0.5-1.2 mT.

204. The method of numbered paragraph 201, wherein applying an APmagnetic field comprises applying the AP electrical field to the targetbody area according to at least one of a treatment duty cycle and afield strength duty cycle.

205. The method of numbered paragraph 204, wherein the treatment dutycycle comprises alternating periods of an on-time in which the APmagnetic field is applied to the target tissue, and an off-time in whichthe AP magnetic field is not applied to the target tissue.

206. The method of numbered paragraph 204, wherein the field strengthduty cycle comprises alternating periods in which the AP magnetic fieldis applied to the target tissue for a first time period at a first fieldstrength followed by a second time period at a second field strength.

207. The method of numbered paragraph 201, wherein the AP magnetic fieldcomprises a bimodal magnetic field frequency distribution comprising afirst variable AP magnetic field that varies the magnetic fieldfrequency between a first lower lim it and a first upper limit and asecond variable AP magnetic field that varies the magnetic fieldfrequency between a second lower limit and a second upper limit.

208. The method of numbered paragraph 201, wherein the AP magnetic fieldcomprises at least one of a variable frequency and a variable fieldstrength.

209. The method of numbered paragraph 201, further comprisingadministering to the patient at least one additional anti-cancer therapyselected from an anti-cancer drug, a radiation therapy, and TTF therapy.

210. The method of numbered paragraph 209, wherein administering a TTFtherapy comprises applying at least one AC electrical field to thetarget tissue, wherein the AC electrical field comprises a frequency of50-500 kHz and an electric field strength of about 10-1000 V/m.

301. A system for treating cancer cells in a target body area of apatient comprising:

-   -   at least one electromagnetic coil coupled to a target body area;        and    -   a controller for controlling the at least one electromagnetic        coil to generate and apply to the target body area an AP        magnetic field having a frequency of 0.5-500 kHz and a field        strength of 0.05-5 mT, wherein the AP magnetic field selectively        affects the cancer cells to achieve at least one of damaging the        cancer cells, inhibiting the growth of the cancer cells,        reducing tumor size, inhibiting angiogenesis, or preventing        metastasis of the cancer cells, while leaving non-cancer cells        substantially unharmed.

302. The system of numbered paragraph 301, wherein the cancer cells areone of breast cancer cells, lung cancer cells, lung carcinoid tumorcells, thymic cancer cells, tracheal cancer cells, pancreatic cancercells, liver cancer cells, stomach cancer cells, kidney cancer cells,ovarian cancer cells, colon cancer cells, rectal cancer cells, prostatecancer cells, throat cancer cells, thyroid cancer cells, mouth cancercells, nose cancer cells, and salivary gland cancer cells.

303. The system of numbered paragraph 302 wherein the at least oneelectromagnetic coil is coupled to the target body area by a retainingelement during the application of the AP magnetic field to the targetbody area.

304. The system of numbered paragraph 303, wherein the cancer cells arebreast cancer cells, and the retaining element is a wearable garmentselected from a bra, a shirt, and a vest.

305. The system of numbered paragraph 303, wherein the cancer cells areselected from lung cancer, lung carcinoid tumors, thymic malignancies,tracheal tumors, pancreatic cancer, liver cancer, stomach cancer, kidneycancer, ovarian cancer, colon cancer and rectal cancer, and theretaining element is a wearable garment selected from a bra, a shirt, avest, and a jacket.

306. The system of numbered paragraph 303, wherein the cancer cells arelower-body cancer cells selected from prostate cancer cells, ovariancancer cells, colon cancer cells, and rectal cancer cells, and theretaining element is an undergarment.

308. The system of numbered paragraph 301 wherein the at least oneelectromagnetic coil is coupled to the target body area by a retainingelement during the application of the AP magnetic field to the targetbody area

309. The system of numbered paragraph 308 wherein the retaining elementis selected from a bra, a shirt, a vest, a jacket, an undergarment, anda bandage.

310. The system of numbered paragraph 301, wherein the at least oneelectromagnetic coil comprises a plurality of electromagnetic coilscoupled to the target body area to obtain a desired magnetic fielddistribution in the target body area.

311. The system of numbered paragraph 301, further comprising: anelectromagnetic shield for shielding at least one non-target body areaof the patient's body from exposure to the AP magnetic field.

401. A system for treating cancer cells in a target area of a patient'sbody comprising:

-   -   at least one electromagnetic coil coupled to a target body area;        and    -   apply to the target body area an alternating polarity (AP)        magnetic field having a frequency of 5 Hz-500 kHz and a field        strength of 0.05-5 mT, wherein the AP magnetic field selectively        affects the cancer cells to achieve at least one of damaging the        cancer cells, inhibiting the growth of the cancer cells,        reducing tumor size, inhibiting angiogenesis, or preventing        metastasis of the cancer cells, while leaving non-cancer cells        substantially unharmed.

402. The system of numbered paragraph 401, further comprising:

-   -   a power supply for supplying power to said electromagnetic coil.

The particular embodiments disclosed above are illustrative only, as theinvention may be modified and practiced in different but equivalentmanners apparent to those skilled in the art having the benefit of theteachings herein. Embodiments of the present invention disclosed andclaimed herein may be made and executed without undue experimentationwith the benefit of the present disclosure. While the invention has beendescribed in terms of particular embodiments, it will be apparent tothose of skill in the art that variations may be applied to systems andapparatus described herein without departing from the concept, spiritand scope of the invention. Examples are all intended to benon-limiting. It is therefore evident that the particular embodimentsdisclosed above may be altered or modified and all such variations areconsidered within the scope and spirit of the invention, which arelimited only by the scope of the claims.

What is claimed is:
 1. A system for treating cancer cells in a targetbody area of a patient comprising: an alternating polarity (AP) magneticfield generator; at least one AP electromagnetic coil coupled to the APmagnetic field generator and adapted to be coupled to the target bodyarea; and a controller for controlling the AP magnetic field generatorand the at least one AP electromagnetic coil, wherein the controller isadapted to cause the AP magnetic field generator and the at least one APmagnetic coil to generate and apply to the target body area an APmagnetic field having a frequency of 0.5-500 kHz and a field strength of0.2-5 mT, wherein the AP magnetic field selectively affects the cancercells to prevent metastasis of the cancer cells, while leavingnon-cancer cells substantially unharmed.
 2. The system of claim 1,wherein the cancer cells are one of breast cancer cells, lung cancercells, lung carcinoid tumor cells, thymic cancer cells, tracheal cancercells, pancreatic cancer cells, liver cancer cells, stomach cancercells, kidney cancer cells, ovarian cancer cells, colon cancer cells,rectal cancer cells, prostate cancer cells, throat cancer cells, thyroidcancer cells, mouth cancer cells, nose cancer cells, and salivary glandcancer cells.
 3. The system of claim 1, wherein the at least one APelectromagnetic coil is coupled to the target body area by a retainingelement during the application of the AP magnetic field to the targetbody area.
 4. The system of claim 3, wherein the cancer cells are breastcancer cells, and the retaining element is a wearable garment selectedfrom a bra, a shirt, a vest, a jacket, a hat, an undergarment, and abandage.
 5. The system of claim 3, wherein the cancer cells are braincancer cells, and the retaining element is a wearable garment comprisesa garment.
 6. The system of claim 5, wherein the garment comprises ahat.
 7. The system of claim 3, wherein the cancer cells are selectedfrom lung cancer, lung carcinoid tumors, thymic malignancies, trachealtumors, pancreatic cancer, liver cancer, stomach cancer, kidney cancer,ovarian cancer, colon cancer and rectal cancer, and the retainingelement is a wearable garment selected from a bra, a shirt, a vest, anda jacket.
 8. The system of claim 1, wherein the controller is adapted tocause the AP magnetic field generator and the at least one AP magneticcoil to apply the AP magnetic field to the target body area during aperiod in which the patient is being treated with one or more of achemotherapy and an immunotherapy.
 9. The system of claim 1 wherein thecontroller is adapted to cause the AP magnetic field generator and theat least one AP magnetic coil to generate and apply to the target bodyarea an AP magnetic field having a frequency within the range of 25-400kHz.
 10. The system of claim 1, wherein the at least one APelectromagnetic coil comprises a plurality of AP electromagnetic coilscoupled to the target body area to obtain a desired magnetic fielddistribution in the target body area.
 11. The system of claim 1, furthercomprising: an electromagnetic shield for shielding at least onenon-target body area of the patient's body from exposure to the APmagnetic field.
 12. A magnetic field therapy system for treating cancercells in a target body area of a patient, comprising: an alternatingpolarity (AP) magnetic field generator; one or more AP electromagneticcoils coupled to the AP magnetic field generator and adapted to becoupled to the target body area, wherein each AP electromagnetic coilmay be energized by an electrical signal from the AP magnetic fieldgenerator to generate an AP magnetic field having at least a firstfrequency of 0.5-400 kHz and a first field strength of 0.2-5 mT, whereinthe AP magnetic field selectively affects the cancer cells to preventmetastasis of the cancer cells, while leaving non-cancer cellssubstantially unharmed; and a controller to control at least one of thefirst frequency and the first field strength of the AP magnetic fieldgenerated by the one or more AP electromatic coils.
 13. The system ofclaim 12, further comprising a power supply for supplying power to saidone or more AP electromagnetic coils.
 14. The system of claim 12,wherein the one or more AP electromagnetic coils are coupled to thetarget body area by a retaining element adapted to maintain theelectromagnetic coil in a desired position relative to the target bodyarea, and the retaining element is selected from a garment and abandage.
 15. The system of claim 14, wherein the at least oneelectromagnetic coil comprises a plurality of AP electromagnetic coils,and the retaining element comprises a bra adapted to maintain theplurality of AP electromagnetic coils in a desired position relative tobreast tissue.
 16. The system of claim 14, wherein the at least one APelectromagnetic coil comprises a plurality of AP electromagnetic coils,and the retaining element comprises a hat adapted to maintain theplurality of electromagnetic coils in a desired position relative tobrain tissue.
 17. The system of claim 13, further comprising a retainingelement, wherein the at least one AP electromagnetic coil, the retainingelement, the power supply, and the controller are each wearable by theuser, and wherein the system comprises an ambulatory treatment systemcapable of applying the AP magnetic field to the cancer cells while thepatient is non-stationary.
 18. The system of claim 12, wherein thecontroller comprises a timing control module to control the one or moreelectromagnetic coil to perform at least one of: applying the APmagnetic field continuously to the target body area for a firsttreatment period; applying the AP magnetic field intermittently for asecond treatment period in alternating on time periods in which the APmagnetic field is applied to the target body area, followed by off timeperiods in which the AP magnetic field is not applied to the target bodyarea; applying the AP magnetic field intermittently for one or morecircadian treatment periods based on circadian rhythms of the patient;and applying the AP magnetic field intermittently for one or more thirdtreatment periods at defined times of day.
 19. The system of claim 12,wherein the controller comprises a frequency control module to controlthe one or more electromagnetic coil to perform at least one of:applying an AP magnetic field having a single frequency of 0.5-400 kHzto the target body area; applying an AP magnetic field having afrequency of 0.5-400 kHz that varies in a defined pattern; applying anAP magnetic field having multiple simultaneous frequencies of 0.5-400kHz; and applying an AP magnetic field having a bimodal magnetic fieldfrequency distribution comprising a first variable AP magnetic fielddistribution that varies the magnetic field frequency between a firstlower limit and a first upper limit and a second variable AP magneticfield distribution that varies the magnetic field frequency between asecond lower limit and a second upper limit.
 20. The system of claim 18,wherein the frequency control module further controls the one or more APelectromagnetic coil to apply an AP magnetic field having at least oneof: a frequency of 0.5-400 kHz that varies randomly; a frequency thatvaries in a Gaussian distribution in one or more ranges within the rangeof 0.5-400 kHz; a frequency that varies in a non-Gaussian distributionin one or more ranges within the range of 0.5-400 kHz.